Ultrastructural changes in motor endplates of the lumbrical muscles of rats induced by a microsomal Ca2+ ATPase inhibitor, 2,5-di(tert-butyl)-1,4-hydroquinone.
Female Wistar rats were treated orally for 5 days with 80 mg/kg body weight of 2,5-di(tert-butyl)-1,4-hydroquinone (DTBHQ), a microsomal Ca2+ ATPase inhibitor. Motor endplates of the lumbrical muscles were examined by light and electron microscopy. There was a decrease in body weight in the treated rats from the first day after administration, and toxic signs appeared after the third day, such as adoption of a prone position, salivation, lacrymation, and an abnormal gait and/or muscle weakness. No remarkable macroscopic or light microscopic changes were noted in the lumbrical muscles as well as other peripheral nerves of hind legs of the treated rats killed 1 day after the last DTBHQ treatment. Ultrastructurally, neurotoxicity characterized by loss of synaptic vesicles and mitochondria in the motor endplates, and by destruction of the motor terminals was detected in the lumbrical muscles of the treated rats. These results strongly indicate that DTBHQ targets the motor endplates in the rat lumbrical muscles and suggest that the resultant damage is responsible for the appearance of neurological signs, such as an abnormal gait and loss of muscle control.
Mitsumori
K
K
Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.
Imazawa
T
T
Onodera
H
H
Takahashi
M
M
Kitajima
S
S
Inoue
T
T
Kurokawa
Y
Y
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005684:Gait / Q000187:drug effects; D006614:Hindlimb; D006873:Hydroquinones / Q000008:administration & dosage / Q000633:toxicity*; D008854:Microscopy, Electron; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000473:pathology; D009045:Motor Endplate / Q000187:drug effects* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000294:innervation*; D051381:Rats; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000187:drug effects / Q000473:pathology
D004791:Enzyme Inhibitors; D006873:Hydroquinones; C019359:2,5-di-tert-butylhydroquinone; D000252:Calcium-Transporting ATPases